Alternative polyadenylation

Polynucleotides o The common polynucleotides are represented by "poly" which precedes the repeating unit symbolized by one-letter sjnnbols for nucleosides thus poly A, poly d(A-T), and poly (A,C) are for polyadenylate, alternating copolymer of dA and dT, and random copolymer of A and C, respectively. 

Figure 37-13. Mechanisms of alternative processing of mRNA precursors. This form of RNA processing involves the selective inclusion or exclusion of exons, the use of alternative 5 donor or 3 acceptor sites, and the use of different polyadenylation sites.

In addition to affecting the efficiency of promoter utilization, eukaryotic cells employ alternative RNA processing to control gene expression. This can result when alternative promoters, intron-exon splice sites, or polyadenylation sites are used. Occasionally, heterogeneity within a cell results, but more commonly the same primary transcript is processed differendy in different tissues. A few examples of each of these types of regulation are presented below. 

Fig. 1.46. Alternative polyadenylation in the expression of calcitonin genes of rat. The primary transcript of the calcitonin gene possesses two polyadenylation sites. One site is nsed in the processing of RNA in the thyroid, another site in the brain, and yet another in nerve tissne. The translation of the two mRNAs creates two pre-hormones, from which two different polypeptide hormones (calcitonin and the calcitonin-related peptide", or CGRP) are created via proteolysis.

FIGURE 26-19 Two mechanisms for the alternative processing of complex transcripts in eukaryotes, (a) Alternative cleavage and polyadenylation patterns. Two poly(A) sites, A, and A2, are shown. 

Certain pre-mRNAs contain more than one set of signal sequences for 3 end cleavage and polyadenylation. In some cases, the location of the alternative polyadenylation sites is such that, depending on the site chosen, particular exons may be lost or retained in the subsequent splicing reactions (Fig. 7). Here the effect is to change the coding capacity of the final mRNA so that different proteins are produced depending on the polyadenylation site used. In other... 

Zieger B, Haahimoto Y, Ware J. Alternative expression of platdd glycoprotein lb(b) mRNA from an adjacent 5 gene with an imperfect polyadenylation signal sequence. J Clin Invest 19 99 520-5. 

Formation of Alternative mRNA by Alternative Polyadenylation and by Alternative Splicing... 

Some pre-mRNAs carry several polyadenylation signals on their 3 -end. Depending upon which signal is used for the polyadenylation, various mRNAs can be formed from a single primary transcript (Fig. 1.41). The mechanism of alternative polyadenylation offers the possibility to form cell- and tissue-specific mRNAs from the same primary transcript. It is still unkown how the cell decides which poly-A signal to use. 

Kornfeld, K., Saint, R.B., Beachy, P.A., Harte, P.J., Peattie, D.A., Hogness, D.S. 1989. Structure and expression of a family of Ultrabithorax mRNAs generated by alternative splicing and polyadenylation in Drosophila. Genes Dev. 3, 243-258. 

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